Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase
View abstract on PubMed
Summary
This summary is machine-generated.Metformin, a diabetes drug, was found to protect heart cells from damage and prevent the worsening of heart failure in dogs by activating AMP-activated protein kinase (AMPK). This suggests metformin could be a new heart failure therapy.
Area Of Science
- Cardiology
- Pharmacology
- Molecular Biology
Background
- Metformin is known to activate AMP-activated protein kinase (AMPK).
- AMPK activation has shown cardioprotective effects against ischemia/reperfusion injury.
- AMPK is also activated in animal models of heart failure.
Purpose Of The Study
- To investigate if metformin decreases cardiomyocyte apoptosis.
- To determine if metformin attenuates the progression of heart failure in dogs.
- To explore the role of AMPK activation in metformin's effects on heart failure.
Main Methods
- Cultured cardiomyocytes were exposed to hydrogen peroxide (H2O2) with or without metformin, and cell death was assessed.
- Dogs were induced into heart failure using rapid ventricular pacing.
- Metformin was administered orally to dogs with heart failure, and cardiac function, AMPK phosphorylation, nitric oxide levels, and insulin resistance were measured.
Main Results
- Metformin protected cardiomyocytes from H2O2-induced cell death via AMPK activation.
- In dogs with heart failure, metformin significantly improved left ventricular fractional shortening and left ventricular end-diastolic pressure compared to vehicle.
- Metformin promoted AMPK and endothelial nitric oxide synthase phosphorylation, increased plasma nitric oxide, and improved insulin resistance, decreasing apoptosis and improving cardiac function.
Conclusions
- Metformin attenuated oxidative stress-induced cardiomyocyte apoptosis and prevented heart failure progression in dogs.
- These effects were associated with the activation of AMPK.
- Metformin presents potential as a novel therapeutic agent for heart failure.